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A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (RNA-seq dataset)

ABSTRACT: Here we identify and characterize a minimal domain within the SS18-SSX fusion oncoprotein hallmark to synovial sarcoma, that exhibits a high-affinity interaction with the nucleosome acidic patch. We find that this region is necessary and sufficient for nucleosome binding, mSWI/SNF (BAF) chromatin remodeling complex targeting, catalytic activity, and activation of cancer-specific gene expression. Moreover, we identify PRC1-mediated H2AUb119 as a further rheostat governing further stability and binding. Together, our results define an unexpected direct bifunctional histone detector on SSX that is responsible for disease-specific chromatin recruitment of a major family of chromatin regulatory complexes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139054 | GEO | 2020/08/04

REPOSITORIES: GEO

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A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (ChIP-seq dataset)

Project description:Here we identify and characterize a minimal domain within the SS18-SSX fusion oncoprotein hallmark to synovial sarcoma, that exhibits a high-affinity interaction with the nucleosome acidic patch. We find that this region is necessary and sufficient for nucleosome binding, mSWI/SNF (BAF) chromatin remodeling complex targeting, catalytic activity, and activation of cancer-specific gene expression. Moreover, we identify PRC1-mediated H2AUb119 as a further rheostat governing further stability and binding. Together, our results define an unexpected direct bifunctional histone detector on SSX that is responsible for disease-specific chromatin recruitment of a major family of chromatin regulatory complexes.

2020-08-04 | GSE139053 | GEO

A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity

Project description:A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity

| PRJNA578154 | ENA

An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [CUT&RUN]

Project description:The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of mSWI/SNF complex, to polycomb repressive complex 1 (PRC1) target genes. Here we show that the SSX C-terminus, via its SSXRD domain, directs SS18-SSX chromatin binding independently of SS18. SSXRD specific targeting is mediated by interaction with H2AK119ub1 and histone MacroH2A with which the fusion overlaps genome wide. Variant Polycomb Repressive Complex 1.1 (PRC1.1) acts as the main depositor of H2AK119ub1 and consequently is required for SS18-SSX occupancy. Importantly, SSX C-terminus not only depends on H2AK119ub1 for localization but also further promotes it and consequently, high H2AK119ub1 levels are acquired during synovial sarcoma development. These results reveal an SS18-SSX/PRC1 autoregulatory feedback-loop that enforces fusion binding and could play a role in a wide-range of cancers and physiological settings where SSX proteins are overexpressed.

2022-06-30 | GSE205954 | GEO

An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [ChIP-seq]

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Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability

Project description:The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of the mSWI/SNF (BAF) complex, to Polycomb repressive complex 1 (PRC1) target genes. Here we show that the ability of SS18-SSX to occupy H2AK119ub1-rich regions is an intrinsic property of its SSX C terminus, which can be exploited by fusion to transcriptional regulators beyond SS18. Accordingly, SS18-SSX recruitment occurs in a manner that is independent of the core components and catalytic activity of BAF. Alternative SSX fusions are also recruited to H2AK119ub1-rich chromatin and reproduce the expression signatures of SS18-SSX by engaging with transcriptional activators. Variant Polycomb repressive complex 1.1 (PRC1.1) acts as the main depositor of H2AK119ub1 and is therefore required for SS18-SSX occupancy. Importantly, the SSX C terminus not only depends on H2AK119ub1 for localization, but also further increases it by promoting PRC1.1 complex stability. Consequently, high H2AK119ub1 levels are a feature of murine and human synovial sarcomas. These results uncover a critical role for SSX-C in mediating gene deregulation in synovial sarcoma by providing specificity to chromatin and further enabling oncofusion binding by enhancing PRC1.1 stability and H2AK119ub1 deposition.

2023-05-24 | GSE233376 | GEO

Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability

2023-05-24 | GSE233375 | GEO

A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (ChIP-seq dataset)

Project description:A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (ChIP-seq dataset)

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A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (RNA-seq dataset)

Project description:A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (RNA-seq dataset)

| PRJNA578158 | ENA

The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma [ATAC-seq]

Project description:Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate a SS transcriptional signature we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

2018-05-31 | GSE114487 | GEO

The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma [RNA-Seq Tumor]

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